Bariatric surgery to cure Type 2 diabetes better understood

Meredith Cohn, The Baltimore Sun

Days after undergoing gastric bypass surgery, Brenda Maker's diabetes was gone — her body producing enough of the hormone insulin to turn sugar into fuel.

It's a phenomenon seen in recent years by doctors who increasingly are using the operation not only to help patients lose weight and improve their health generally but specifically to address the national epidemic of Type 2 diabetes.

Now some researchers at the University of Maryland believe their work may explain why the surgery succeeds, and how a common drug may be used to induce similar effects.

The researchers plan to begin studies with humans this fall, though a pill to cure diabetes may be a long way off, said Steven D. Munger, a professor of anatomy and neurobiology in Maryland School of Medicine who has been working with other researchers on animals models for more than two years.

"If we could find a way of mimicking the anti-diabetes surgery without surgery, it might be a nice alternative and whole new way of therapeutically addressing diabetes," said Munger, whose research recently was published in the American Journal of Physiology – Endocrinology and Metabolism.

"Everyone might not be a candidate or want surgery," he said.

Almost 26 million Americans now have diabetes, most with Type 2, in which the body doesn't produce enough or doesn't process insulin needed to convert sugar and starches to energy, according to the American Diabetes Association. This form of the disease is linked to excessive weight, putting another 79 million in the pre-diabetic category.

Diabetes sufferers have higher rates of heart disease and stroke, high blood pressure, blindness, kidney and nervous system disorders and amputations. The disease is estimated to cost the nation $116 billion a year in direct medical costs.

The diabetes association stops short of recommending surgery but says it should be considered for obese people who have other health problems not controlled with medications and lifestyle changes. The surgery, the group said, carries risks and still requires patients to adhere to significant dietary changes and life-long monitoring.

The type of surgery that seems to work is gastric bypass, which shrinks the stomach considerably and shortens the rest of the digestive system. Studies show the surgery cures diabetes in about 78 percent of patients, usually before weight loss occurs.

No one has been sure why, but a hormone called glucagon-like peptide-1, or GLP-1, has been suspected to play a role for about a decade.

In a person without diabetes, the stomach uses the hormone to warn the pancreas to make insulin when there is an increase in sugar in the blood.

People with Type 2 diabetes have a defect in how the body responds to and produces insulin in the pancreas. Increasing GLP-1 levels can help increase insulin production to levels where it can control blood sugar, and gastric bypass seems to increase GLP-1 production.

Munger and fellow researchers' studies on rats seem to show that the sugar-sensing mechanism also can be triggered in the large intestine. It's an unlikely place, because the primary site for production of the GLP-1 hormone is the small intestine.

The researchers now are trying to figure outhow to trigger the mechanism without surgery.

A leading candidate, glyburide, is a drug currently used for diabetes treatment. It's cheap and can be taken orally, but can cause the pancreas to produce too much insulin, which can make blood sugar drop too low. So there are efforts to replace it.

Munger said scientists who regularly work with pharmaceuticals may be able to target the drug to the large intestine where it could prompt GLP-1 production or they may find a new drug to directly spur insulin production. First, he and fellow researchers need to show the mechanism works in humans and not just rats.

Something worked for Maker after her surgery. But an explanation was less important than addressing her diabetes before it caused more severe health problems. She already had high blood pressure, sleep apnea and acid reflux.

In addition to curing her diabetes and other health problems, she's also lost 117 pounds, and went from size 22 to size 10. She recently completed her first 5K road race.

She said she probably would have considered a pill to avoid the surgery, which she had in November, but now she's glad she didn't. It would have done nothing for those extra pounds.

"I was really headed down the wrong path," said Maker, a 48-year-old paralegal who lives in Linthicum. "My biggest thing, though, I'm bad at taking pills and I didn't want to have to take pills anymore. And I got way more out of surgery then I every thought I would."

Still, she said the surgery is a major commitment. There was six months of work on her diet and a psychiatric evaluation before the dietitian, psychologist and surgeon decided she was a good candidate. Surgery also carries risks. And then the lifestyle changes include eating frequent, very small meals, which is not something she said overweight people are used to doing.

A pill would help many other people, she believes.

Her doctor at Saint Agnes Hospital, Dr. Andrew Averbach, agreed and said he'd like to be able to offer a pill to patients who can't or wouldn't fair well with surgery because of the required lifestyle changes. Diabetes can return in patients who regain weight.

For now, he's not expecting any let up in the number of people who come in for gastric bypass surgery or other bariatric surgery, to control weight and health problems. The Saint Agnes center, one of the region's busiest, does about 650 such surgeries a year.

For those who are willing to make lifestyle changes, Averbach said it's cheaper today to do surgery than treat diabetes long-term because of all of the complications and other related health problems.

"Bariatric surgery is very safe but a pill it usually safer," he said. "If they can come up with this magic pill it would be nice."